What Is the Minimum Clinically Important Change in Negative Symptoms of Schizophrenia? PANSS Based Post-hoc Analyses of a Phase III Clinical Trial
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Introduction Minimum clinically important difference (MCID) is a measure that defines the minimum amount of change in an objective score of a clinical test that must be reached for that change to be clinically noticeable. We aimed to find the MCID for patients with predominantly negative symptoms of schizophrenia at its earliest occurrence. Methods Data of a 26-week long, double-blind study with 454 patients [Positive and Negative Symptom Scale Negative Factor Score (PANSS-FSNS) ≥24, Positive and Negative Symptom Scale Positive Factor Score (PANSS-FSPS) ≤ 19] treated with cariprazine 4.5 mg/d or risperidone 4 mg/d were analyzed. The Clinical Global Impression—Improvement scale was used to quantify minimum improvement (CGI-I = 3) and no clinical change (CGI-I = 4) on the PANSS-FSNS, and the MCID was estimated with the following methods: as the mean PANSS-FSNS changes corresponding to the first instance of minimal improvement across all visits (MCID1); as the difference between the PANSS-FSNS change associated with the first instance and the PANSS-FSNS changes associated with the last recorded clinically unchanged status across all visits (MCID2); with the effect size approach (MCID3); as the Youden Index based cut-off value between no clinical change and minimal improvement (MCID4); as the relative likelihood of minimal improvement (MCID5). Results The MCID1 and MCID2 resulted in, respectively, a 3.8-point (18.5%) and a 1.5-point (7.3%) decrease from baseline severity on the PANSS-FSNS. Greater values were required for the MCID at later evaluation times. The cut-off between minimum improvement and no clinical change defined by the Youden Index was a−3-point (15%) change in the PANSS-FSNS. The effect size approach indicated the 1.5-point difference between minimally improved and unchanged patients to be a medium effect (ES = 0.6). Conclusion Applying different methods led to different results, ranging between 7.3 and 18.5% improvement from the baseline for the MCID at its earliest occurrence in patients with predominantly negative symptoms of schizophrenia.
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The mean reductions in negative symptoms (2.8 intervention, 2.4 control) surpassed the minimum clinically significant difference of 1.5 points.
“These reductions surpassed the minimum clinically significant difference of 1.5 points,61 signifying a medium-sized effect and underline the effectiveness of the comprehensive TAU in reducing both positive and negative symptomatology while suggesting a possible additional benefit of YoGI.”
From Yoga-Based Group Intervention for Inpatients with Schizophrenia Spectrum Disorders—Feasibility, Acceptability, and Preliminary Outcomes of a Rater-Blinded Randomized Controlled Trial. (2026) · cites this paper as [61]
The Abstract Results and the Results table report a 1.5-point MCID2 estimate, and the distribution-based Results describe that difference as a medium effect (ES = 0.6). But 1.5 points is the difference between minimally improved and unchanged patients, not an unqualified threshold for interpreting the citing study’s 2.8- and 2.4-point reductions. The paper also reports other estimates, including a 3.8-point change from baseline at minimal improvement. (LLM, conf=0.85)
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- Authors
- Czobor, P., Sebe, B., Acsai, K., Barabássy, Á., Laszlovszky, I., Németh, G., Furukawa, T. A., & Leucht, S.
- Affiliations
- Semmelweis University (HU)
- Gedeon Richter (Hungary) (HU)
- Kyoto University (JP)
- Technical University of Munich (DE)
- Corresponding author
- Czobor, Pál
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2022-04-25
- Volume
- 13
- Pages
- 816339-816339
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC9083222
- OpenAlex
- W4224313524
- Cited by
- 20
- References
- 35
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 4
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, cc-by)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Health Systems, Economic Evaluations, Quality of Life
- Keywords
- minimal clinically important difference, schizophrenia, negative symptoms, cariprazine, risperidone, PANSS, early treatment response, Youden index, effect size, antipsychotic drugs
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